Epidemiologic Notes and Reports Persistent, Generalized Lymphadenopathy among Homosexual Males

Since October 1981, cases of persistent, generalized lymphadenopathy--not attributable to previously identified causes--among homosexual males have been reported to CDC by physicians in several major metropolitan areas in the United States. These reports were prompted by an awareness generated by ongoing CDC and state investigations of other emerging health problems among homosexual males (1).

In February and March 1982, records were reviewed for 57 homosexual men with lymphadenopathy seen at medical centers in Atlanta, New York City, and San Francisco. The cases reviewed met the following criteria: 1) lymphadenopathy of at least 3 months' duration, involving 2 or more extra-inguinal sites, and confirmed on physical examination by the patient's physician; 2) absence of any current illness or drug use known to cause lymphadenopathy; and 3) presence of reactive hyperplasia in a lymph node, if a biopsy was performed.

The 57 patients had a mean age of 33 years and the following characteristics: all were male; 81% were white, 15% black, and 4% Hispanic; 83% were single, 6% married, and 11% divorced; 86% were homosexual, 14% bisexual. The median duration of lymphadenopathy was 11 months. Ninety-five percent of patients had at least 3 node chains involved (usually cervical, axillary, and inguinal). Forty-three patients had had lymph node biopsies showing reactive hyperplasia. Approximately 70% of the patients had some constitutional symptoms including fatigue, 70%; fever, 49%; night sweats, 44%; and weight loss of greater than or equal to 5 pounds, 28%. Hepatomegaly and/or splenomegaly was noted among 26% of patients.

Recorded medical histories for the 57 patients suggested that the use of drugs such as nitrite inhalants, marijuana, hallucinogens, and cocaine was common. Many of these patients have a history of sexually transmitted infections (gonorrhea 58%, syphilis 47%, and amebiasis 42%). Of 30 patients skin-tested for delayed hypersensitivity response, 8 were found to be anergic on the basis of at least 2 antigens other than purified protein derivative (PPD).

Immunologic evaluation performed at CDC for 8 of the above patients demonstrated abnormal T-lymphocyte helper-to-suppressor ratios (0.9) for 2 patients. Since this review, immunologic evaluations at CDC of 13 additional homosexual males with lymphadenopathy from Atlanta and San Francisco revealed 6 with ratios of 0.9. The normal range of T-lymphocyte helper-to-suppressor ratios established in the CDC laboratory for healthy heterosexual patients is 0.9-3.5 (mean of 2.3). The normal range is being established for apparently healthy homosexual males.

Since the initiation of this study, 1 patient with lymphadenopathy has developed Kaposi's sarcoma. Reported by D Mildvan, MD, U Mathur, MD, Div of Infectious Diseases, Beth Israel Medical Center, R Enlow, MD, Rheumatology Dept, Hospital for Joint Diseases, D Armstrong, MD, J Gold, MD, C Sears, MD, B Wong, MD, AE Brown, MD, S Henry, MD, Div of Infectious Disease, B Safai, MD, Dermatology Svc, Dept of Medicine, Z Arlin, MD, Div of Hematology, Memorial Sloan-Kettering Medical Center, A Moore, MD, C Metroka, MD, Div of Hematology-Oncology, L Drusin, MD, MPH, Dept of Medicine, The New York Hospital-Cornell Medical Center, I Spigland, MD, Div of Virology, Montefiore Hospital and Medical Center, DC William, MD, St. Luke's-Roosevelt Hospital Center, F Siegal, MD, Dept of Medicine, J Brown, MD, Dept of Neoplastic Diseases, Mt. Sinai Medical Center, J Wallace, MD, Dept of Medicine, St. Vincent's Hospital and Medical Center, D Sencer, MD, SM Friedman, MD, YM Felman, MD, New York City Dept of Health, R Rothenberg, MD, State Epidemiologist, New York State Dept of Health; RK Sikes, DVM, State Epidemiologist, Georgia Dept of Human Resources; W Owen, MD, Bay Area Physicians for Human Rights, S Dritz, MD, C Rendon, Bureau of Communicable Disease Control, San Francisco Dept of Public Health, J Chin, MD, State Epidemiologist, California Dept of Health Svcs; J Sonnabend, MD, Uniformed Svcs University of Health Sciences, Bethesda, E Israel, MD, State Epidemiologist, Maryland State Dept of Health and Mental Hygiene; Special Studies Br, Center for Environmental Health, Div of Viral Diseases, Div of Host Factors, Center for Infectious Diseases, Field Svcs Div, Epidemiology Program Office, Task Force on Kaposi's Sarcoma and Opportunistic Infections, Office of the Centers Director, CDC.

Editorial Note

Editorial Note: The report above documents the occurrence of cases of unexplained, persistent, generalized lymphadenopathy among homosexual males. There are many known causes of generalized lymphadenopathy including viral infections (e.g., hepatitis B, infectious mononucleosis, cytomegalovirus infection, rubella), tuberculosis, disseminated Mycobacterium avium-intracellulare, syphilis, other bacterial and fungal infections, toxoplasmosis, connective tissue disorders, hypersensitivity drug reactions, heroin use, and neoplastic diseases (including leukemia and lymphoma) (2). Causes for the persistent lymphadenopathy among patients discussed above were sought but could not be identified.

This unexplained syndrome is of concern because of current reports of Kaposi's sarcoma (KS) and opportunistic infections (OI) that primarily involve homosexual males (1,3). Epidemiologic characteristics (age, racial composition, city of residence) of the homosexual patients with lymphadenopathy discussed here are similar to those of the homosexual KS/OI patients. Thirty-two (44%) of 73 Kaposi's sarcoma patients and 14 (23%) of 61 Pneumocystis carinii pneumonia patients reported to CDC in the period mid-June 1981-January 1982 had a history of lymphadenopathy before diagnosis (3). Mycobacterium avium-intracellulare (an opportunistic agent) has been isolated from the lymph nodes of a homosexual patient (4). Moreover, the findings of anergy and depressed T-lymphocyte helper-to-suppressor ratios in some of the patients with lymphadenopathy suggest cellular immune dysfunction. Patients with KS/OI have had severe abnormalities of cellular immunity (5,6). The relationship between immunologic findings for patients with lymphadenopathy and patients with KS/OI remains to be determined.

Although these cases have been identified and defined on the basis of the presence of lymphadenopathy, this finding may be merely a manifestation of an underlying immunologic or other disorder that needs to be characterized further. Virologic and immunologic studies of many of these patients are currently under way. An analysis of trends in incidence for lymphadenopathy over the past several years is being conducted to determine whether this syndrome is new and whether homosexual males are particularly affected. Results of these studies and follow-up of these patients are necessary before the clinical and epidemiologic significance of persistent, generalized lymphadenopathy among homosexual males can be determined. Homosexual male patients with unexplained, persistent, generalized lymphadenopathy should be followed for periodic review.

References

1. CDC. Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men--New York City and California. MMWR 1981;30:305-8.

2. Wintrobe MM. Clinical hematology. 8th ed. Philadelphia: Lea and Febiger, 1981: 1279-81.

3. CDC. Task Force on Kaposi's Sarcoma and Opportunistic Infections. Epidemiologic aspects of the current outbreak of Kaposi's sarcoma and opportunistic infections. N Engl J Med 1982;306:248-52.

4. Fainstein V, Bolivar R, Mavligit G, Rios A, Luna M. Disseminated infection due to Mycobacterium avium-intracellulare in a homosexual man with Kaposi's sarcoma. J Infect Dis 1982;145:586.

5. Gottleib M, Schroff R, Schanker H, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men. N Engl J Med 1981;305:1425-31.

6. Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med 1981;305:1431-8.

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